There is growing body of data evaluating the value of PI3K/AKT/mTOR inhibitors in CRC (e.g., BEZ235, NVP-BEZ235, OSI-027, everolimus, MK-2206, KRX-0401, BYL719, and BKM120).
PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5<sup>+</sup> CRC stem cells survival and proliferation, from which lead to chemotherapy resistance.
Finally, we used an agonist (740Y-P) of the PI3K/Akt signaling pathway; function assays showed that PlncRNA-1 exerted its effects by targeting the PI3K/Akt signaling pathway in CRC.
Parent genes of these DEAS play a important role in regulating CRC-related processes such as protein kinase activity (FDR<0.0001), PI3K-Akt signaling pathway (FDR = 0.0024) and p53 signaling pathway (FDR = 0.0143).
Taken together, our data suggest that both FUT5 and FUT6 can promote the development of CRC via the PI3K/Akt signalling pathway, which is regulated by miR-125a-3p. miR-125a-3p may serve as a predictive biomarker and a potential therapeutic target in CRC treatment.
We report that WDR5 is a novel factor in the metastasis of CRC by triggering epithelial-mesenchymal transition (EMT) process in response to the PI3K/AKT signaling pathway.
Furthermore, PLD1 inhibition suppressed growth of colorectal cancer activated by the Wnt/β-catenin and PI3K signaling pathways.<b>Conclusions:</b> These results suggest that PLD1 linked to ICAT mediates molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways and thus could be proposed as a novel colorectal cancer prognostic biomarker.
Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF.
Taken together, our data indicate that lncRNA AB073614 acts to prevent CRC progression by affecting the PI3K/AKT signaling pathway, and may be useful as a novel prognostic or treatment agent for CRC.
We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration.
Moreover, overexpression of TPD52 in CRC SW480 cells showed an increased cell migration (P = 0.023) and invasion (P = 0.012) through inducing occurrence of epithelial-mesenchymal transition (EMT) and activating focal adhesion kinase (FAK)-mediated integrin signalling and PI3K⁄Akt signalling.Whereas TPD52-depleted cells showed the reverse effect.
This response was also confirmed with <sup>18</sup>F-FDG microPET/CT imaging.<b>Implications:</b> Spheroid models and transgenic mice suggest that dual PI3K/mTOR inhibition is a potential treatment strategy for <i>APC</i> and <i>PIK3CA</i>-mutant colorectal cancers.
MiR-422a directly targets 3'-UTR of the AKT1 and MAPK1, down-regulation of miR-422a led to the activation of Raf/MEK/ERK and PI3K/AKT signaling pathways to promote cell proliferation in CRC.
In summary, we demonstrated that both colorectal adenoma and CRC are monoclonal in origin, and the CRCs further diversified into different subclones with heterogeneous mutation profiles accumulating in GPCR, PI3K-Akt and FGFR signaling pathways.